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Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated −7 (mda-7)/interleukin-24 (IL-24) gene

Cancer Gene Therapy volume 12, pages 238–247 (2005)Cite this article

A Corrigendum to this article was published on 16 February 2005

Abstract

We have previously reported that overexpression of the melanoma differentiation-associated gene -7 (mda-7) using a replication-defective adenovirus (Ad-mda7), results in tumor-specific growth suppression and induction of apoptosis in wide variety of cancer cells. In the present study, we investigated the antitumor activity of Ad-mda7 and the underlying mechanism in human prostate cancer cells and normal prostate epithelial cells. Overexpression of MDA-7 induced significant (P=.001) suppression of cell growth and apoptosis in prostate cancer cells (DU 145, LNCaP, and PC-3). In normal prostate epithelial cells (PrEC) some degree of growth inhibition but not apoptosis was observed. However, the inhibitory effects in normal cells were less compared to tumor cells. Growth inhibitory effects were mediated by the intracellular and not by extracellular MDA-7 protein. Molecular effectors that are involved in Ad-mda7-mediated tumor killing included activation of the caspase cascade, and the induction of G2 phase cell cycle arrest through the inhibition of Cdc25C pathway. These results demonstrate the mechanisms by which Ad-mda7 exerts its antitumor activity in human prostate cancer cells. The antitumor activity combined with previously reported antiangiogenic and proimmune properties of Ad-mda7 can serve as a potential therapeutic agent for treatment of primary and disseminated prostate cancer.

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Acknowledgements

We thank Alma Vega for assistance in the preparation of the manuscript. This work was supported in part by the Texas Higher Education Coordinating Board ATP/ARP Grant 003657-0078-2001 (RR), the Cancer Center Support Grant CA16672, an NCI Grant R43 CA86587 (SC), the Institutional Research Grant (RR), the WM Keck Gene Therapy grant (RR), and by a sponsored research agreement with Introgen Therapeutics, Inc. (RR).

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Authors and Affiliations

  1. Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA

    Yuji Saito, Ryo Miyahara, Began Gopalan, Anya Litvak, Satoshi Inoue, Manish Shanker, Cynthia D Branch, Jack A Roth & Rajagopal Ramesh

  2. Introgen Therapeutics, Houston, Texas, 77030, USA

    Abner M Mhashilkar & Sunil Chada

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  1. Yuji Saito
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Correspondence to Rajagopal Ramesh.

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Saito, Y., Miyahara, R., Gopalan, B. et al. Selective induction of cell cycle arrest and apoptosis in human prostate cancer cells through adenoviral transfer of the melanoma differentiation-associated −7 (mda-7)/interleukin-24 (IL-24) gene. Cancer Gene Ther 12, 238–247 (2005). https://doi.org/10.1038/sj.cgt.7700780

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